Basel, Switzerland-based Roche and Isis Pharmaceuticals of Carlsbad, Calif., have formed an alliance to develop treatments for Huntington's disease (HD) based on Isis' antisense oligonucleotide (ASO) technology.

The alliance combines Isis' antisense expertise with Roche's scientific expertise in developing neurodegenerative therapeutics. In addition, Isis and Roche will be collaborating to combine Isis' ASOs and Roche's proprietary "brain shuttle" program with the objective of increasing the brain penetration of ASOs with systemic administration.

Initially, research will focus on Isis' lead drug candidate that blocks production of all forms of the huntingtin (HTT) protein, the protein responsible for HD and thus has the potential to treat all HD patients. Isis is also conducting research into treatments that specifically block production of the disease-causing forms of the HTT protein which has the potential to treat subsets of HD patients. In parallel, Roche will combine its proprietary brain shuttle technology with Isis ASO technology that, if successful, will also allow systemic administration of antisense drugs to treat asymptomatic patients.

Roche will make an upfront payment of $30 million to Isis, with total payments related to license fee and pre- and post-licensing milestone payments reaching potentially $362 million, including up to $80 million in potential commercial milestone payments. In addition, Isis will receive tiered royalties on sales of the drugs. Roche has the option to license the drugs from Isis through the completion of the first phase I trial. Prior to option exercise, Isis is responsible for the discovery and development of an antisense drug targeting HTT protein. If Roche exercises its option, it will be responsible for global development, regulatory and commercialization activities for all drugs arising out of the collaboration.

"Central to the partnership is Roche's brain shuttle program, which we see as highly complementary to Isis' drug development work,” said Shafique Virani, global head neuroscience, cardiovascular and metabolism at Roche Partnering. “This dual track development program ensures whichever candidate compound proves to be most promising—Isis' lead target or Roche's brain shuttle version—can be taken forward to pivotal clinical trials."

B. Lynne Parshall, chief operating officer of Isis, said, "By partnering our more complex and nuanced research and development programs earlier in development, like our Huntington's disease CNS program, we add value and resources with partners that bring unique benefits."

CHDI Foundation, a non-profit foundation exclusively dedicated to the development of therapies that slow the progression of HD, provided financial and scientific support to Isis' HD drug discovery program through a development collaboration with Isis. Together Isis and CHDI demonstrated that antisense compounds can be used to inhibit the production of HTT protein in both brain and peripheral tissues, and that the inhibition of normal HTT protein was well tolerated. Over time, CHDI will be reimbursed for its support of Isis' program out of the milestone payments received by Isis. CHDI will receive $1.5 million associated with the signing of the Roche agreement. CHDI will continue to provide advice to Isis and Roche on the development of antisense drugs to treat patients with HD.